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Ewing’s sarcoma that has spread from the initially affected bone to one or more sites in the body, distant from the site of origin, is called metastatic. The most common site to which Ewing’s sarcoma spreads, or metastasizes, is the lungs. Metastatic Ewing’s is typically difficult to control, though patients with lung metastases have a better prognosis than patients with other distant metastases.

The following is a general overview of treatment for metastatic Ewing’s sarcoma. Treatment may consist of surgery, radiation systemic therapy or a combination. Multi-modality treatment is treatment using two or more techniques and is increasingly recognized as an important approach for increasing a patient’s chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. 

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​The multi-modality approach to treatment for metastatic Ewing’s sarcoma requires that patients be treated by a multi-disciplinary team consisting of the primary care physician, an orthopedic surgeon experienced in bone tumors, a pathologist, radiation oncologists, pediatric oncologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others. An experienced team is best found in specialty cancer centers that treat many patients with Ewing’s sarcoma. 

Systemic Therapy

Systemic therapy is any treatment directed at destroying cancer cells throughout the body. Many patients have small amounts of cancer that have spread away from their site of origin or remain after surgery. These cancer cells are difficult to detect and are referred to as micro-metastatic or minimal residual disease (MRD). Their presence is what causes a sarcoma's recurrence following local treatment with surgery and/or radiation therapy. An effective systemic treatment is needed to cleanse the body of MRD to improve a patient’s duration of survival and potential for cure.

Systemic Therapy: Precision Cancer Medicines, Chemotherapy & Immunotherapy

Precision cancer medicines, chemotherapy and immunotherapy are all forms of systemic treatment that circulate in the blood and can destroy cancer cells throughout the body. Chemotherapy, once the only systemic therapy is increasingly being complimented by more targeted precision cancer medicines and immunotherapy. The use of precision medicines and immunotherapy is determined by performing biomarker tests that identify which therapy will be most effective. Cancer patients should undergo NGS testing to look for biomarkers that can be targeted with precision medicines. Precision cancer medicines and immunotherapies can be used both instead of and in addition to chemotherapy.


Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs, and can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill. Chemotherapy is not “targeted” to the cancer and acts more generally in the body’s cells which can result in more side effects.

High-dose ifosfamide chemotherapy has shown superior survival benefit over other standard chemotherapy regimens for patients with recurring or refractory primary Ewing sarcoma,

Ifosfamide was compared to a combination of topotecan and cyclophosphamide (TC) chemotherapy. Median overall survival was 15.4 months for ifosfamide versus 10.5 months versus TC, and 1-year overall survival was 55% versus 45%, respectively.1

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Immunotherapy is also a standard treatment for cancer and can be used alone or in combination with other systemic therapies. Immunotherapy either works to stimulate your immune system to attach the cancer or remove obstacles that prevent your immune system from working normally.

Precision Cancer Medicines

Not all cancer cells are alike. They may differ from one another based on what genes have mutations. Molecular testing can be performed to test for certain genetic mutations or the proteins they produce, and the results can help identify newer precision cancer medicines that target cancer cells with specific genetic mutations.

The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving the growth of that specific cancer. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

Precision medicines been approved for the treatment of advanced sarcomas or are being developed in clinical trials. In order to identify which drugs can be used your physician needs to have NGS-biomarker testing performed on the cancer tissue or blood. The following are known targets for available precision cancer medicines. 

Strategies to Improve Treatment

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies and are ongoing at major sarcoma treatment centers.

High-Dose Chemotherapy with Autologous Stem Cell Transplantation: Several small pilot studies have evaluated the use of high-dose chemotherapy with autologous stem cell transplantation in patients with relapsed or recurrent Ewing’s sarcoma The results of these studies suggest that this treatment may be an effective salvage treatment (treatment given after the cancer has not responded to other treatments) for selected patients with metastatic Ewing’s sarcoma. Researchers from the University of Washington treated 55 consecutive patients with a relapse of Ewing’s sarcoma between 1985 and 2002. The five year survival of chemotherapy responsive patients was 46 percent versus 0 percent for those that did not respond. Overall survival of chemotherapy-responsive patients was 75 percent among those who received an autologous stem cell transplant and 20 percent among those who did not receive an autologous stem cell transplant.3-8

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Precision Cancer Medicines: Several precision cancer medicines might be an option for treating specific cancer growth driving mutations. Families should discuss NGS-biomarker testing with their physician.


  1. ASCO 2022. Abstract LBA2. Presented June 5, 2022.
  2. Miser JS, Krailo MD, Tarbell NJ, et al. Treatment of metastatic Ewing’s sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide—a Children’s Cancer Group and Pediatric Oncology study. Journal of Clinical Oncology 2004;22:2873-2876.
  3. Grier H, Krailo M, Tarbell N, et al. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. New England Journal of Medicine. 2003;348:694-701.
  4. High histologic and overall response to dose intensification of ifosfamide, carboplatin, and etoposide with cyclophosphamide, doxorubicin, and vincristine in patients with high-risk Ewing’s sarcoma family tumors:The Bambino Gesu Children’s Hospital experience. Cancer2005;106:1838-1845.
  5.  Navid F, Santana VM, Billups CA, et al. Concomitant administration of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for high-risk sarcomas: the St. Jude Children’s Hospital experience. Cancer 2006;106:1846-1856.
  6. Fraser CJ, Weigel BJ, Perentisis JP, et al. Autologous stem cell transplantation for high-risk sarcoma and other pediatric solid tumors. Bone Marrow Transplantation 2006;37:175-181.
  7. Megachemotherapy followed by autologous stem cell transplantation in children with Ewing’s sarcoma. Pediatric Transplantation 2005;9:618-621.d Megachemotherapy followed by autologous stem cell transplantation in children with Ewing’s sarcoma. Pediatric Transplantation 2005;9:618-621
  8. Daw NC, Furman WL, Stewart CF, et al. Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Childrens Oncology Group Study. Journal of Clinical Oncology 2005;23:6172-6180.
  9. McAllister WR and Lessnick SL. The potential for molecular therapeutic targets in Ewing’s sarcoma. Current Treatment Options in Oncology 2005;6:461-471.